Compound 48/80 is commonly used to study the mechanism of histamine release, as a standard of comparison for other histamine liberators, and in studies requiring the exhaustion of mast cell amines. However, the structure and mode of action of this very potent substance are not known. In preliminary studies, using gel filtration and mass spectroscopy, we have shown that the most generally accepted structure is incorrect. In other studies involving protozoa, fungi, and bacteria, we have found that compound 48/80 also has potent antimicrobial activity. Recently, we have isolated two components of 48/80 which possess histamine-releasing and antimicrobial activity separately. Based on preliminary structural evidence, we have synthesized an analog which has seven times the histamine-liberating activity of 48/80 itself. We propose to determine the molecular structures of the most active of these histamine liberators, to synthesize labelled derivatives in order to isolate and study the structure and function of the mast cell receptor, and to design specific antagonists to these and other histamine releasing substances. We further propose to isolate and determine the structures of the antimicrobial components of 48/80 which do not possess histamine-releasing activity, and to conduct related structure-activity studies with the goal of developing a new type of antimicrobial agent.